ID PEPD_ECOLI Reviewed; 485 AA.
AC P15288;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 24-JAN-2024, entry version 184.
DE RecName: Full=Cytosol non-specific dipeptidase;
DE EC=3.4.13.18;
DE AltName: Full=Aminoacyl-histidine dipeptidase;
DE AltName: Full=Beta-alanyl-histidine dipeptidase;
DE AltName: Full=Carnosinase;
DE AltName: Full=Cysteinylglycinase;
DE AltName: Full=Peptidase D;
DE AltName: Full=Xaa-His dipeptidase;
DE Short=X-His dipeptidase;
GN Name=pepD; Synonyms=pepH; OrderedLocusNames=b0237, JW0227;
OS Escherichia coli (strain K12).
OC Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PARTIAL PROTEIN SEQUENCE.
RC STRAIN=K12;
RX PubMed=1695895; DOI=10.1128/jb.172.8.4641-4651.1990;
RA Henrich B., Monnerjahn U., Plapp R.;
RT "Peptidase D gene (pepD) of Escherichia coli K-12: nucleotide sequence,
RT transcript mapping, and comparison with other peptidase genes.";
RL J. Bacteriol. 172:4641-4651(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RA Takemoto K., Mori H., Murayama N., Kataoka K., Yano M., Itoh T.,
RA Yamamoto Y., Inokuchi H., Miki T., Hatada E., Fukuda R., Ichihara S.,
RA Mizuno T., Makino K., Nakata A., Yura T., Sampei G., Mizobuchi K.;
RT "Systematic sequencing of the Escherichia coli genome: analysis of the 4.0
RT - 6.0 min (189,987 - 281,416bp) region.";
RL Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RA Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M.,
RA Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D.,
RA Namath A., Oefner P., Roberts D., Schramm S., Davis R.W.;
RT "Sequence of minutes 4-25 of Escherichia coli.";
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-56, AND PROTEIN SEQUENCE OF 2-13.
RC STRAIN=K12;
RX PubMed=2651887; DOI=10.1007/bf00427031;
RA Henrich B., Schroeder U., Frank R.W., Plapp R.;
RT "Accurate mapping of the Escherichia coli pepD gene by sequence analysis of
RT its 5' flanking region.";
RL Mol. Gen. Genet. 215:369-373(1989).
RN [7]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=355237; DOI=10.1128/jb.135.2.603-611.1978;
RA Miller C.G., Schwartz G.;
RT "Peptidase-deficient mutants of Escherichia coli.";
RL J. Bacteriol. 135:603-611(1978).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBSTRATE SPECIFICITY, ACTIVITY
RP REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=7988883; DOI=10.1111/j.1574-6968.1994.tb07215.x;
RA Schroeder U., Henrich B., Fink J., Plapp R.;
RT "Peptidase D of Escherichia coli K-12, a metallopeptidase of low substrate
RT specificity.";
RL FEMS Microbiol. Lett. 123:153-159(1994).
RN [9]
RP FUNCTION.
RX PubMed=11157967; DOI=10.1128/jb.183.4.1489-1490.2001;
RA Suzuki H., Kamatani S., Kim E.-S., Kumagai H.;
RT "Aminopeptidases A, B, and N and dipeptidase D are the four
RT cysteinylglycinases of Escherichia coli K-12.";
RL J. Bacteriol. 183:1489-1490(2001).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-296, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=K12 / JW1106, and K12 / MG1655 / ATCC 47076;
RX PubMed=18723842; DOI=10.1074/mcp.m800187-mcp200;
RA Zhang J., Sprung R., Pei J., Tan X., Kim S., Zhu H., Liu C.F.,
RA Grishin N.V., Zhao Y.;
RT "Lysine acetylation is a highly abundant and evolutionarily conserved
RT modification in Escherichia coli.";
RL Mol. Cell. Proteomics 8:215-225(2009).
RN [11]
RP FUNCTION IN PEPTIDE DEGRADATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / JM101 / ATCC 33876 / DSM 3948 / NCIMB 11926;
RX PubMed=20067529; DOI=10.1111/j.1574-6968.2009.01879.x;
RA Hayashi M., Tabata K., Yagasaki M., Yonetani Y.;
RT "Effect of multidrug-efflux transporter genes on dipeptide resistance and
RT overproduction in Escherichia coli.";
RL FEMS Microbiol. Lett. 304:12-19(2010).
CC -!- FUNCTION: Dipeptidase with broad substrate specificity. Requires
CC dipeptide substrates with an unblocked N-terminus and the amino group
CC in the alpha or beta position. Non-protein amino acids and proline are
CC not accepted in the C-terminal position, whereas some dipeptide amides
CC and formyl amino acids are hydrolyzed. Also shows cysteinylglycinase
CC activity, which is sufficient for E.coli to utilize cysteinylglycine as
CC a cysteine source. {ECO:0000269|PubMed:11157967,
CC ECO:0000269|PubMed:20067529, ECO:0000269|PubMed:355237,
CC ECO:0000269|PubMed:7988883}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of dipeptides, preferentially hydrophobic
CC dipeptides including prolyl amino acids.; EC=3.4.13.18;
CC Evidence={ECO:0000269|PubMed:355237, ECO:0000269|PubMed:7988883};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:7988883};
CC Name=Co(2+); Xref=ChEBI:CHEBI:48828;
CC Evidence={ECO:0000269|PubMed:7988883};
CC Note=Binds 2 Zn(2+) ions per subunit. Can also use Co(2+).
CC {ECO:0000269|PubMed:7988883};
CC -!- ACTIVITY REGULATION: Inhibited by metal chelators.
CC {ECO:0000269|PubMed:7988883}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 9. {ECO:0000269|PubMed:7988883};
CC Temperature dependence:
CC Optimum temperature is 37 degrees Celsius.
CC {ECO:0000269|PubMed:7988883};
CC -!- INTERACTION:
CC P15288; P60560: guaC; NbExp=3; IntAct=EBI-542419, EBI-544491;
CC P15288; P15034: pepP; NbExp=4; IntAct=EBI-542419, EBI-554801;
CC -!- DISRUPTION PHENOTYPE: A quadruple peptidase disruption (pepA, pepB,
CC pepD and pepN) does not grow in M9 minimal medium, grows better when
CC supplemented with casamino acids (PubMed:20067529).
CC {ECO:0000269|PubMed:20067529}.
CC -!- SIMILARITY: Belongs to the peptidase M20C family. {ECO:0000305}.
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DR EMBL; M34034; AAA16111.1; -; Unassigned_DNA.
DR EMBL; U70214; AAB08657.1; -; Genomic_DNA.
DR EMBL; U00096; AAC73341.1; -; Genomic_DNA.
DR EMBL; AP009048; BAA77906.1; -; Genomic_DNA.
DR EMBL; X14790; CAA32892.1; -; Genomic_DNA.
DR PIR; JU0300; JU0300.
DR RefSeq; NP_414772.1; NC_000913.3.
DR RefSeq; WP_001292994.1; NZ_SSZK01000050.1.
DR AlphaFoldDB; P15288; -.
DR SMR; P15288; -.
DR BioGRID; 4259765; 43.
DR BioGRID; 849407; 2.
DR DIP; DIP-10456N; -.
DR IntAct; P15288; 69.
DR STRING; 511145.b0237; -.
DR MEROPS; M20.007; -.
DR iPTMnet; P15288; -.
DR SWISS-2DPAGE; P15288; -.
DR jPOST; P15288; -.
DR PaxDb; 511145-b0237; -.
DR EnsemblBacteria; AAC73341; AAC73341; b0237.
DR GeneID; 945013; -.
DR KEGG; ecj:JW0227; -.
DR KEGG; eco:b0237; -.
DR PATRIC; fig|1411691.4.peg.2046; -.
DR EchoBASE; EB0689; -.
DR eggNOG; COG2195; Bacteria.
DR HOGENOM; CLU_028526_0_0_6; -.
DR InParanoid; P15288; -.
DR OMA; KGGYPGW; -.
DR OrthoDB; 9773892at2; -.
DR PhylomeDB; P15288; -.
DR BioCyc; EcoCyc:EG10695-MONOMER; -.
DR BioCyc; MetaCyc:EG10695-MONOMER; -.
DR PRO; PR:P15288; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0103046; F:alanylglutamate dipeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0016805; F:dipeptidase activity; IMP:EcoCyc.
DR GO; GO:0070573; F:metallodipeptidase activity; IDA:EcoCyc.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:EcoCyc.
DR GO; GO:0008270; F:zinc ion binding; IDA:EcoCyc.
DR GO; GO:0043171; P:peptide catabolic process; IGI:EcoliWiki.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd03890; M20_pepD; 1.
DR Gene3D; 3.40.630.10; Zn peptidases; 2.
DR InterPro; IPR002933; Peptidase_M20.
DR InterPro; IPR011650; Peptidase_M20_dimer.
DR InterPro; IPR001160; Peptidase_M20C.
DR NCBIfam; TIGR01893; aa-his-dipept; 1.
DR PANTHER; PTHR43501; CYTOSOL NON-SPECIFIC DIPEPTIDASE; 1.
DR PANTHER; PTHR43501:SF1; CYTOSOL NON-SPECIFIC DIPEPTIDASE; 1.
DR Pfam; PF07687; M20_dimer; 1.
DR Pfam; PF01546; Peptidase_M20; 1.
DR PIRSF; PIRSF016599; Xaa-His_dipept; 1.
DR PRINTS; PR00934; XHISDIPTASE.
DR SUPFAM; SSF53187; Zn-dependent exopeptidases; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cobalt; Dipeptidase; Direct protein sequencing; Hydrolase;
KW Metal-binding; Metalloprotease; Protease; Reference proteome; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:2651887"
FT CHAIN 2..485
FT /note="Cytosol non-specific dipeptidase"
FT /id="PRO_0000185354"
FT ACT_SITE 78
FT /evidence="ECO:0000250"
FT ACT_SITE 145
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 76
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 115
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 115
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 146
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 169
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 457
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT MOD_RES 296
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:18723842"
SQ SEQUENCE 485 AA; 52915 MW; CD870032876460E1 CRC64;
MSELSQLSPQ PLWDIFAKIC SIPHPSYHEE QLAEYIVGWA KEKGFHVERD QVGNILIRKP
ATAGMENRKP VVLQAHLDMV PQKNNDTVHD FTKDPIQPYI DGEWVKARGT TLGADNGIGM
ASALAVLADE NVVHGPLEVL LTMTEEAGMD GAFGLQGNWL QADILINTDS EEEGEIYMGC
AGGIDFTSNL HLDREAVPAG FETFKLTLKG LKGGHSGGEI HVGLGNANKL LVRFLAGHAE
ELDLRLIDFN GGTLRNAIPR EAFATIAVAA DKVDVLKSLV NTYQEILKNE LAEKEKNLAL
LLDSVANDKA ALIAKSRDTF IRLLNATPNG VIRNSDVAKG VVETSLNVGV VTMTDNNVEI
HCLIRSLIDS GKDYVVSMLD SLGKLAGAKT EAKGAYPGWQ PDANSPVMHL VRETYQRLFN
KTPNIQIIHA GLECGLFKKP YPEMDMVSIG PTITGPHSPD EQVHIESVGH YWTLLTELLK
EIPAK
//
